Many of the investigations in this genetic epidemiology project arise from observations in families at high risk of cancer or in other etiologic studies. Analyses of the data from a case-control study of ovarian cancer in Israel of the Jewish population revealed that parity appeared protective among both carriers and noncarriers of founder BRCA1/2 mutations. Although oral contraceptive use appeared protective among noncarriers, among carriers oral contraceptive use conferred no protection. Prognostic factors and secondary malignancies were evaluated in a retrospective study of 88 consecutive cases of childhood medulloblastoma. Overall survival was 59% at 5 years and 52% at 10 years. The risk of second neoplasms was significantly increased in this cohort of patients. Within an American case-control study of cutaneous melanoma, significant evidence for familial heterogeneity was found for melanoma. Few individuals had family members with pancreatic cancer. CDKN2A mutations were only rarely seen in this population. As a follow-up to a recently completed DCEG comprehensive case-control study of adults with brain tumors, a family-based study of the parents, siblings and adult children of the 480 eligible glioma cases is being conducted. Relatives are interviewed about personal and family medical history and other risk factors and are asked to provide buccal cells as a source of DNA. The relatives will be used as controls for the glioma cases in association studies and in analyses to evaluate the roles of genetic susceptibility and environmental exposures on the risk of gliomas and etiologically related tumors. A case-control study of 183 incident melanoma cases and 179 controls conducted in North-Eastern Italy identified the strongest risk factors for non-familial melanoma and determined how the combinations of these factors contributed to melanoma risk in Mediterranean populations. Presence of dysplastic nevi, low propensity to tan, light eye and light skin color were all highly associated with melanoma risk after adjustment for age, gender, and pigmentation characteristics. A chart showing melanoma risk associated with multiple combinations of these factors was created to identify patients who would most benefit from preventive measures in Mediterranean populations. The counter-matching design was used to examine the power for detecting gene-environment interactions. The sensitivity and specificity of the surrogate measures, the frequencies of the genetic and environmental exposures, and the value of the interaction effect were the most important parameters for determining efficiency. Feasibility was also most dependent on the exposure frequencies and interaction effect. Although still unable to study very rare factors, counter-matching appeared more appropriate than most traditional epidemiologic methods for studying interactions involving rare factors. Linked data from cancer, population, and hospital discharge registries are being obtained from collaborators in Denmark and Sweden which includes cases of lymphoproliferative (LP) cancers including Hodgkin's disease, Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, and Multiple Myeloma, matched controls, and first degree relatives of cases and controls. Hypotheses to examine increased risks of LP cancers and autoimmune disorders among relatives of cases will be tested.